Asthma and Food Allergy

Asthma is a chronic inflammatory disorder afflicting the lower respiratory tract, characterized by a narrowing of the air passages. Roughly one in ten American children has asthma, and an estimated 6.5 million children under the age of 18 have been diagnosed with the condition. The prevalence of asthma is increasing, particularly amongst children, and the World Health Organization (WHO) estimates that each year 15 million disability-adjusted life-years are lost, and approximately 250,000 asthma deaths are reported [2]. Similarly, food allergy affects around 5.9 million children in the US, or 8% of children under 18 years of age. Moreover, nearly 2 out of every 5 children with food allergy have a history of severe reactions. In these cases, accidental exposure to an allergenic substance may result in breathing difficulties, an abrupt drop in blood pressure, and even death [3]. Both asthma and food allergies have serious implications, particularly amongst pediatric victims, and in a significant number of children, the two conditions are associated. Diagnosis with both asthma and food allergy presents a risk factor for fatal anaphylactic reactions.

Asthma and food allergy present examples of Type I Hypersensitivity (type I HS), in which an individual’s immune system incorrectly recognizes substances that are normally harmless as threatening invaders. As a result, an immune response is inappropriately mounted against them. The triggers for type I HS are referred to as allergens because they are antigens that cause allergy. Type I hypersensitivity reactions occur rapidly following the introduction of allergen in the body, and a particular subset of antibodies, called IgE, become implicated in the pathology of the immune response. These IgE antibodies, in cases of allergy, are directed against the allergen particles (including components of pollen, pet dander, or nuts, for example). During an asthma attack, inhalation of allergy-inducing substances or environmental triggers causes inflammation of the air passages, such that airways become constricted and breathing becomes quite difficult. In an allergic reaction to a food allergen (i.e. peanuts, soy, milk, eggs, wheat, or fish), a variety of possible symptoms may manifest, depending on whether the inflammatory response is induced in the mouth, the gastrointestinal tract, or enters the blood stream becoming systemic or provoking symptoms in a separate location of the body. In both asthma and food allergy, the exposure to allergen stimulates mast cells, a type of cell involved in inflammatory processes, to release the contents of their granules (cellular vesicles that contain substances like histamine, serotonin, and proteases). These fast-acting mediators are responsible for the rapid onset of initial symptoms associated with type I hypersensitivities because they are preformed within the cell, ready to be released upon activation. Histamine promotes blood vessel dilation and permeability, or leakiness, mucus production, itching, sneezing, and contraction of bronchial smooth muscle. Similarly, serotonin is associated with vasodilation and bronchial smooth muscle contraction. Proteases released by the mast cells are also involved in mucus production, as well as in increased blood pressure.

Approximately 4-6 hours following onset of these reactions, various white blood cells (leukocytes) migrate to the allergen-laden tissue. Especially significant in this stage of allergic reaction are eosinophils, which possess receptors on their surfaces that bind to IgE antibodies coating the allergen. Upon interaction of these receptors with the IgE-allergen complexes, the eosinophils undergo degranulation, similarly to the mast cells described above. The contents released from the eosinophil granules include leukotrienes, platelet-activating factor (PAF), major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin; when these substances diffuse into the surrounding tissue, they cause substantial damage to cells. Because the cells that line the airways exhibit elevated sensitivity to these mediators, symptoms of asthma are attributed predominantly to eosinophil activation during allergic reaction. This pathology is known as eosinophilic airway inflammation and is considered a distinguishing feature of asthma. Furthermore, worsening airway inflammation in pediatric cases of asthma is correlated with exacerbating symptoms. While asthma severity is known to be associated with eosinophilic airway inflammation, as well as with a co-diagnosis of food allergy, it had not been determined whether this type of inflammation is exacerbated in asthmatic children with food allergies, until quite recently. A study published in Pediatric Allergy and Immunology examined the hypothesis that eosinophilic airway inflammation is higher in children with both food allergies and asthma [1].

Kulkarni and colleagues first evaluated food and aeroallergen sensitization in the participants through history, skin prick tests for common aeroallergens and food substances, and, in the food allergy group, through the presence of IgE in serum. The results showed that all of the subjects with food allergies were additionally sensitized to at least one aeroallergen, and sensitization to house dust mites was the highest, followed by pollen, pet dander, and fungi. Sensitization to dust mites was also elevated in asthmatic children without food allergies. No statistically significant differences were found between aeroallergen sensitization in asthmatic patients with or without food allergies. The authors then measured exhaled nitric oxide through FeNO analysis, a surrogate marker of eosinophilic inflammation, and found that children with both asthma and food allergies had significantly higher FeNO median than asthmatic children without food allergy. Next, the authors determined eosinophil counts across participants. To accomplish this, the authors evaluated induced sputum eosinophil differential count, which is attained by hypertonic saline inhalation for a period no longer than 12-15 minutes, while every several minutes during that time frame children are asked to produce sputum to be collected for eosinophil cell count. The sputum eosinophil count was found to be substantially higher in children with both asthma and food allergy than children with asthma only and was not dependent on the type of food allergy involved or seasonal changes (some children were tested during autumn and winter months and others during spring and summer months). Through further data analysis (multiple linear regression), the authors concluded that allergy to food substances in asthmatic children was the only factor significantly associated with the observed eosinophilic airway inflammation increases. Among the cell types measured through the induced sputum differential count, including eosinophils, macrophages, neutrophils, and lymphocytes, eosinphil counts exhibited by far the most substantial differences between the asthma with food allergies group and asthma without food allergies group.

The findings in this study confirm that children with asthma and food allergies have higher eosinophil counts and FeNO than those who do not have food allergies. Airway inflammation in children with food allergies may be a result of inhaling food allergens, or alternatively due to a systemic reaction following food allergen exposure. This study provides evidence that airway inflammation seen in children with food allergies may be a result of sensitization to aeroallergens as well, such that the hypersensitivity reaction to food allergen manifests in tissues lining the airways. Children who require intensive care intervention for life-threatening asthmatic attacks are considerably more likely to have food allergies than children with less severe asthma. Therefore, the results described above have significant implications for treatment protocols in pediatric asthma patients with food allergies. Controlling eosinophilic airway inflammation may reduce the occurrence of flair ups or attacks in these individuals more so than corticosteroids. Treatment regimens that include lipoxygenase antagonists, which block the generation of leukotrienes, may be beneficial, as leukotrienes promote eosinophil infiltration during the late phase of the allergic response. Further research will be necessary to examine the effectiveness of both controlling eosinohilic inflammation, as well as monitoring eosinophilic inflammatory markers for guiding treatment and management of food allergy.

Primary Reference

1. Kulkarni N, V. Ragazzo, S. Costella, G. Piacentini, A. Boner, C. O’Callaghan, A. Fiocchi, A. Kantar. 2011. Eosinophilic airway inflammation is increased in children with asthma and food allergies. Pediatr Allergy Immunol. Doi: 10.1111/j.1399-3038.2011.01226.x .

References

2. Akinbami, L., J. Moorman, X. Liu. 2011. Asthma prevalence, health care use, and mortality: United States, 2005-2009. National Health Statistics Reports 32: 1-16.

3. Gupta, R. S, E. Springston, M. Warrier, B. Smith, R. Kumar, J. Pongracic, J. Holl. 2011. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics. DOI: 10.1542/peds.2011-0204.